ROX Index and ROX Vector to Predict Nasal High Flow / Continuous Positive Airway Pressure Failure in Neonates

Nasal continuous positive airway pressure (CPAP) and Nasal High Flow (NHF) therapy are two primary therapies for the treatment of respiratory distress in newborns. However, a considerable number of infants, who are initially treated with CPAP and NHF, will develop worsening respiratory failure and eventually require intubation for mechanical ventilation and the administration of surfactant. Infants who fail noninvasive respiratory therapy may suffer the consequences of delayed intubation, surfactant administration and other adverse outcomes. The most challenging decisions in the management of respiratory distress after birth is to decide when to move from a noninvasive respiratory support to invasive mechanical ventilation and give surfactant to decrease pulmonary damage and improve outcomes. There are no clinically adequate predictors of early CPAP failure at the time of admission to the neonatal intensive care unit. Many measurements have been investigated for their ability to predict CPAP failure in infants such as fraction of inspired oxygen (FiO2), partial pressure of oxygen (PaO2), PaO2/FiO2 and the stable micro bubble test as soon as possible after birth. Roca and colleagues first established the ROX index to predict the success of NHF therapy in adults with pneumonia. The ROX index combines three common measurements: FiO2, peripheral oxygen saturation (SpO2) and respiratory rate. Combining the ROX values with the change in the respiratory rate and FiO2 can indicate whether escalation is required. It was proposed that XY plot of the key components of ROX may show the direction of changes in vector form.

The investigators hypothesized that the ROX index and ROX vector can be used for predicting the failure of CPAP and NHF in neonates.

Study Overview

• Status: Recruiting
• Conditions: Predictive Value of Tests
• Intervention / Treatment: Other: Nasal high flow; Other: Continuous Positive Airway Pressure

Detailed Description

The objective is to explore the usefulness of ROX index to predict treatment failure of NHF and CPAP therapies in neonates.

The primary outcome is treatment failure within 72 h after start of the therapy with NHF or CPAP

Treatment failure criteria is reached once an infant is receiving maximal therapy for their treatment (NHF 8 L/min) or CPAP 7 cm H2O plus at least one of:

1. Sustained increase in oxygen requirement ≥50% to maintain peripheral oxygen saturation (SpO2) 90%-94%.
2. Any infant requiring urgent intubation and the subsequent mechanical ventilation, as determined by the physician.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Pavel Mazmanyan, Prof; Phone Number: +374 10 47 23 40; Email: pavelart@gmail.com
• Study Contact Backup: Name: Ella Mirzoyan, MD; Email: ellamirzoyan@gmail.com

Study Locations

• Armenia
  • Yerevan, Armenia
    • Recruiting
    • Erebouni Medical Centre, NICU
    • Contact: Pavel Mazmanyan, Prof; Phone Number: +37410472340; Email: pavelart@gmail.com
  • Yerevan, Armenia
    • Not yet recruiting
    • Republican Institute of Reproductive Health, NICU
    • Contact: Serine Meliksetyan, MD, PhD; Email: serinemn@yahoo.com
  • Yerevan, Armenia
    • Not yet recruiting
    • Research Center of Maternal and Child Health Protection NICU
    • Contact: Anaida Asatryan, MD; Email: asatryanan@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 day (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

neonates with respiratory distress

Description

Inclusion criteria:

• They are admitted to a NICU when <24 h old, AND
• The decision has been made by the attending clinician, to commence or continue (from stabilization at birth) non-invasive respiratory support (this does not include the provision of supplemental oxygen alone), AND
• They have not previously been intubated or received surfactant

Exclusion criteria:

• They immediately require intubation and ventilation (determined by attending clinician), OR
• They already satisfy 'treatment failure' criteria, OR
• They have a known major congenital anomaly or air leak

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Predicting treatment failure of Nasal High Flow in newborns; newborns with respiratory distress treated with NHF	Other: Nasal high flow; Newborns with respiratory distress treated with NHF.
Predicting treatment failure of Continuous Positive Airway Pressure in newborns; newborns with respiratory distress treated with CPAP	Other: Continuous Positive Airway Pressure; Newborns with respiratory distress treated with CPAP.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants requiring escalation of treatment	Treatment failure criteria is reached once an infant is receiving maximal therapy for their treatment (NHF 8 L/min) or CPAP 7 cm H2O plus at least one of: Sustained increase in oxygen requirement above ≥50% to maintain peripheral oxygen saturation (SpO2) 90%-94%.; Any infant requiring urgent intubation and the subsequent mechanical ventilation, as determined by the physician.	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with death	Death before discharge from the hospital	Monitored for the entire stay in hospital, until discharge, up to 6 months
Number of participants with pneumothorax	Pneumothorax determined by chest radiograph	Monitored for the entire stay in hospital, until discharge, up to 6 months
Number of participants with Necrotizing enterocolitis stage II-III	Necrotizing enterocolitis determined by abdominal radiograph	Monitored for the entire stay in hospital, until discharge, up to 6 months
Number of participants with Intra-ventricular hemorrhage	Intra ventricular hemorrhage confirmed by head ultrasound	Monitored for the entire stay in hospital, until discharge, up to 6 months
Number of participants with Bronchopulmonary dysplasia	Bronchopulmonary dysplasia	through study completion, up to 6 months
Number of participants with Cystic Periventricular Leukomalacia	Cystic Periventricular Leukomalacia confirmed by ultrasound	Monitored for the entire stay in hospital, until discharge, up to 6 months
Number of participants with PDA needed surgical treatment	Patent ductus arteriosus	Monitored for the entire stay in hospital, until discharge, up to 6 months
Number of participants with ROP needing laser treatment	Retinopathy of prematurity needing laser treatment	Monitored for the entire stay in hospital, until discharge, up to 6 months
Number of participants requiring blood transfusion	Blood transfusion	Monitored for the entire stay in hospital, until discharge, up to 6 months
total number of days on O2 / noninvasive ventilation	total number of days on O2 / noninvasive ventilation	Monitored for the entire stay in hospital, until discharge, up to 6 months
Total number days in the hospital	Total number days in the hospital	Monitored for the entire stay in hospital, until discharge, up to 6 months

Collaborators and Investigators

• Sponsor: Erebouni Medical Center
• Collaborators: Fisher and Paykel Healthcare
• Investigators: Principal Investigator: Pavel Mazmanyan, Prof, Head of Department of Neonatology YSMU

Publications and helpful links

General Publications

• Roca O, Caralt B, Messika J, Samper M, Sztrymf B, Hernandez G, Garcia-de-Acilu M, Frat JP, Masclans JR, Ricard JD. An Index Combining Respiratory Rate and Oxygenation to Predict Outcome of Nasal High-Flow Therapy. Am J Respir Crit Care Med. 2019 Jun 1;199(11):1368-1376. doi: 10.1164/rccm.201803-0589OC.
• Roca O, Messika J, Caralt B, Garcia-de-Acilu M, Sztrymf B, Ricard JD, Masclans JR. Predicting success of high-flow nasal cannula in pneumonia patients with hypoxemic respiratory failure: The utility of the ROX index. J Crit Care. 2016 Oct;35:200-5. doi: 10.1016/j.jcrc.2016.05.022. Epub 2016 May 31.
• Fuchs H, Lindner W, Leiprecht A, Mendler MR, Hummler HD. Predictors of early nasal CPAP failure and effects of various intubation criteria on the rate of mechanical ventilation in preterm infants of <29 weeks gestational age. Arch Dis Child Fetal Neonatal Ed. 2011 Sep;96(5):F343-7. doi: 10.1136/adc.2010.205898. Epub 2011 Jan 30.
• Tatkov S. Nasal High-Flow Therapy: Role of FiO2 in the ROX Index. Am J Respir Crit Care Med. 2019 Jul 1;200(1):115-116. doi: 10.1164/rccm.201902-0376LE. No abstract available.
• Tatkov S. ROX vector to complement ROX index during nasal high flow therapy of hypoxemic patients. J Crit Care. 2020 Aug;58:129. doi: 10.1016/j.jcrc.2019.08.012. Epub 2019 Oct 18. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2021
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: August 9, 2021
• First Submitted That Met QC Criteria: August 30, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): September 24, 2021
• Last Update Submitted That Met QC Criteria: September 19, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: respiratory distress; CPAP; newborn; treatment failure; nasal high flow; neonatal; NHF; ROX
• Other Study ID Numbers: N 6-2/2, 2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No